Numerous studies have linked low bone mass with an increased rate of fracture in patients with osteoporosis. Although low bone mass appears to be fracture permissive, the loss of bone mass alone has proven an inadequate predictor of fracture risk. Additional indicators and mechanisms of fragility must be identified as some individuals with a high bone mass fracture while others with low bone mass do not. In preliminary studies, the significance of bone's morphologic, chemical and physical properties for predicting fracture toughness to cadaver bone from older individuals (> 50 years) was identified. The important features were found to be those associated with bone remodeling: osteon morphology, porosity (density) and microdamage. In the current application, it is proposed to examine bone histomorphology, microdamage and bone mineral content (BMC) of human cortical bone from the proximal femur obtained post-mortem from age groups under-represented in preliminary studies (> 50 years) and from age groups not represented in preliminary studies (young males and females in pre-menopausal females, (<50 years). Using multiple regression analysis, the most important properties for predicting fracture toughness will be identified. An assessment of age related differences in bone toughness and bone properties will be made to determine how these bone features changes over a lifetime and if the relationships among them is the same for each gender. A proposed mechanistic model to predict the influence of bone remodeling parameters on bone toughness will be evaluated using experimental measurements. In addition, fatigue experiments will be used to determine the influence of microdamage accumulation on fracture toughness and whether a damage threshold exists, after which additional damage accumulation is detrimental to the resistance of bone to fracture. A continuum damage model that explains the influence of microdamage on fracture toughness will be developed. These studies will contribute to a fundamental understanding of how bone remodeling features (osteon morphology, porosity (density) and microdamage) contribute to non-traumatic osteoporotic fracture. The identification of specific correlates with a high, or low, resistance to fracture may suggest new clinical approaches for treatments of patients at risk.